Secondary Data Analysis of the Data from Comparison of AMD Treatments Trials

描述（由申请人提供）：拟议项目将利用由美国国家眼科研究所申办的多中心非劣效性临床试验“AMD治疗方法比较试验”（CATT）的综合数据集， 评估雷珠单抗（Lucentis）和贝伐单抗（Avastin）每月治疗或PRN（prore nata）治疗的疗效和安全性。本建议的具体目标不包括CATT研究的主要目标，这些目标已经实现。相反，拟定项目涉及CATT数据集的额外二次分析，以解决以下重要的新目标：（1）描述2年治疗期间随时间推移的视力反应模式，并确定视力的短期反应（1次或3次注射后）是否可预测长期（2年）视力反应。 (2)描述2年治疗期间OCT和荧光素血管造影随时间推移捕获的形态学变化，并评价3个月时的形态学缓解是否可预测2年时的长期形态学缓解。 (3)评估抗VEGF治疗2年后视力和形态学变化之间的相关性。 (4)描述治疗模式，并确定与接受PRN治疗2年的患者治疗次数较少相关的预后因素。 (5)评估基因型-表型与新生血管性AMD的形态学特征和严重程度的相关性。 (6)评价抗凝药物与新生血管性AMD患者视网膜出血的关系。 CATT数据集是进一步评估Lucentis和Avastin对视觉和形态学变化的影响的独特资源，以阐明视觉和形态学反应之间的关联，并确定可能与新生血管性AMD特征相关的因素（遗传和全身药物暴露）。CATT数据集的分析将为治疗眼科医生及其患者提供有用的信息，了解治疗的预期效果，并通过个性化药物帮助监测和优化新生血管性AMD的治疗。非常大的样本量（N=1185），高质量的数据集，以及研究者的丰富经验和高生产力，沿着CATT研究小组的全力支持，支持高风险的可行性和可能性。 建议项目的收益率。

DESCRIPTION (provided by applicant): The proposed project will utilize the comprehensive dataset from the Comparison of Age-related Macular Degeneration (AMD) Treatments Trials (CATT), a multi-center non-inferiority clinical trial, sponsored by the National Eye Institute, to assess the efficacy and safety of ranibizumab (Lucentis) and bevacizumab (Avastin) when treated monthly or PRN (pro re nata). The specific aims of this proposal do not include the major goals of the CATT Study, which were already accomplished. Instead, the proposed project involves additional secondary analysis of the CATT dataset to address the following important new aims: (1) To describe the response pattern of visual acuity over time during the 2 years of treatment, and to determine whether the short-term response of visual acuity (after 1 or 3 injections) predicts the long-term (2 years) visual acuity response. (2) To describe the morphologic changes captured by OCT and fluorescein angiography over time during 2 years of treatment, and to evaluate whether the morphologic responses at 3 months predict the long-term morphologic responses at 2 years. (3) To assess the associations between vision and morphologic changes from anti- VEGF treatment at 2 years. (4) To describe treatment patterns and identify the prognostic factors associated with a low number of treatments in patients treated PRN for 2 years. (5) To assess genotype-phenotype associations with respect to the morphologic features and severity of neovascular AMD at presentation. (6) To evaluate the association of anticoagulation medications with retinal hemorrhage in patients with neovascular AMD. The CATT dataset is a unique resource to further evaluate the effects of Lucentis and Avastin on visual and morphologic changes, to elucidate the association between visual and morphologic responses, and to determine the factors (genetic and systemic drug exposure) that may be associated with features of neovascular AMD at presentation. The analyses of the CATT dataset will provide useful information to the treating ophthalmologists and their patients on what to expect from treatments, and to help monitor and optimize the treatment of the neovascular AMD by personalized medicine. The very large sample size (N=1185), high quality of the dataset, as well as the rich experience and high productivity of the investigators along with the full supports of the CATT Research Group, support the feasibility and likelihood of high yield of the proposed project.